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Abstract

Kaempferia parviflora, also known as black ginger, is a popular medicinal plant among the Southeast Asian community. Recently, there has been increased interest in further exploring the potential health benefits and therapeutic applications of K. parviflora in Malaysia, Thailand's neighboring country. This review provides an overview of current literature regarding K. parviflora's traditional use and literature on efficacy and safety. We found that, traditionally, K. parviflora was used for gastrointestinal disorders, allergies, as sexual stimulants, and body nourishment. K. parviflora demonstrated antioxidant, anti-inflammatory, antiobesity, anticancer, vascular relaxation, and antimicrobial effects. In humans, there is evidence of its general benefits on physical fitness. In conclusion, K. parviflora is a plant with significant potential for various pharmacological applications. The rhizome is most popularly used and investigated, with polymethoxyflavones as the main bioactive phytoconstituent.

Keywords

black ginger herbal medicine kunyit hitam krachai dum flavonoids medicinal properties

Introduction

Kaempferia parviflora, a herbaceous plant belonging to the family Zingiberaceae, is native to Southeast Asia and is also known as black ginger, Thai ginseng, or Krachai Dum to the locals. K. parviflora is a perennial herb that grows up to 90 cm in height. Its inflorescence is white with a purple tinge. Its rhizome is light to dark purple and may also be black. It has one to several leaves, 7 to 20 cm long. This herb carries a characteristic aromatic odor, with a slightly bitter taste.¹ K. parviflora is widely distributed throughout Southeast Asia, India, South China, Malaysia, Thailand, and Laos.² In Thailand, this herb is recognized as one of the top five spearheaded herbal products. Its widespread use and generated income for Thailand is based on anecdotal evidence of efficacy.³

The rhizome of K. parviflora is the most important plant part for medicinal use due to its rich content of phytoconstituents. The therapeutic benefits of K. parviflora have been mostly attributed to the presence of methoxyflavones. Methoxyflavones, structurally defined as 5,7-dimethoxyflavone (DMF), 57,4′-trimethoxyflavone (TMF), and 3,5,7,3′,4′-pentamethoxyflavone (PMF), have been identified as the main components of K. parviflora rhizomes as shown in Figure 1.^4,5

Figure 1.

Structures of three major methoxyflavones of Kaempferia parviflora rhizome.

The DMF compound has been extensively studied for its biological activities, including anti-diabetes,⁶ anti-obesity,^7,8 and anti-inflammatory^9,10; while TMF have potential vasodilator effects evidenced by its ability to elicit concentration-dependent vasorelaxation in the rat aorta, mediated via endothelium-derived nitric oxide,¹¹ which could contribute towards beneficial effects in exercise performance and general physical fitness.¹² The third methoxyflavone, the PMF, can act as a sexual stimulant in men. PMF demonstrated a relaxing effect on isolated human corpus cavernosum tissue via calcium mobilization.¹³ It has also been identified as an important mediator of phosphodiesterase type 5 enzyme (PDE5) phosphodiesterase type 6 enzyme (PDE6) inhibition and vasorelaxation, suggesting potential benefit in the treatment of erectile dysfunction.¹⁴

Hence, Malaysia has made continuous efforts in its local industry to develop herbal products that contain or are based on K. parviflora. There are numerous traditional medicine products containing K. parviflora available in Malaysia, as documented in the QUEST 3 + database managed by the National Pharmaceutical Regulatory Agency (NPRA).¹⁵ Due to the growing interest among local stakeholders in further exploring the potential health benefits and therapeutic applications of K. parviflora in Malaysia, this review was conducted to map the current biomedical research landscape and identify the gaps related to K. parviflora.

Results and Discussion

Results

Traditional Uses of Kaempferia parviflora Rhizome

Most of the published information on the traditional uses of black ginger is centered on Thailand because of the nation's extensive use of the herb. K. parviflora is traditionally used for colic disorder, peptic and duodenal ulcers, relief of impotent symptoms, allergies, asthma, gout, gastrointestinal disorders (eg, diarrhea and dysentery), fungal infections, as well as a tonic for body strengthening and carminative agents.^16–20

Health Benefits of Kaempferia parviflora

Summary of Included Studies

A total of 276 articles were identified from keyword search on published literature. After deduplication, 192 articles were screened based on the inclusion and exclusion criteria. A final 92 articles were included. The screening and article selection process is shown in Figure 2.

Figure 2.

Preferred reporting items for systematic review and Meta-analysis (PRISMA) flow chart of articles inclusion.

Reported Medicinal Properties and Health Benefits

K. parviflora demonstrated various pharmacological properties including antioxidant, anti-inflammatory, antiobesity, anticancer, vascular relaxation, and antimicrobial effects, as well as displaying evidence for general benefits on physical fitness. Among the most studied efficacies include antiobesity, anti-aging in physical and physiological functions, antidiabetic, and benefits in male reproductive and urology (benign prostate hyperplasia systems). Although there were quite a few studies for anticancer properties, these were all in vitro cell studies. For skin health, only preclinical evidence was available.

Clinical Studies

Seven out of the 12 clinical studies included are randomized controlled trials (parallel design). The other study designs are randomized crossover trials (n = 3); open labeled, single-arm interventional trial (n = 1), and single arm pilot trial (n = 1). Most of the clinical studies were conducted on orally administered preparations, except for one which uses transdermal patch for anti-inflammatory effects. A total of eight studies investigated the rhizome plant part while the remaining four studies did not report clearly on the plant part used. Dosage used in clinical studies differs based on preparations and ranged from 90 mg to 360 mg for extracts, 1.35 g for dried powder in capsule, and 12 mg for purified PMF compound. The duration of the studies ranged from two to 12 weeks. The characteristics of included studies and key findings on efficacy are summarized in Table 1.

Table 1.

Details of Clinical Studies of K. parviflora.

Plant part	Formulation	Route, dose, frequency, duration	Study population, age (sample size)	Study design	Summary of efficacy findings	Limitation of study	Author, Year
	A. Anti-inflammatory
Rhizome	Ethanolic extract of K. parviflora extract (2.5-10%) & various volatile oils (5%)	Transdermal, 1 patch, OD, 7 days	Healthy volunteers, 25–60 years (n = 30)	RCT (Parallel)	Significant pain improvement; mean pain threshold increased but pain tolerance unchanged	Short duration of treatment	Tuntiyasawasdikul, 2022 ²¹
	B. Antiobesity
Rhizome	60% ethanol extract of dried powder in capsules (containing DMF 4.07%, TeMF 2.16%, and PMF 4.25%)	Oral, 100 mg, single dose	Healthy volunteers, 21–29 years (n = 20)	RCT (Crossover)	Exhibited antiobesity effect; activated BAT thermogenesis, increased whole-body energy expenditure & reduced body fat deposition	Did not include obesity patient	Matsushita, 2015 ²²
Unclear	K. parviflora extract capsule (details of formulation unclear)	Oral, 150 mg, OD, 12 weeks	Healthy pre-obese subjects aged 20 - below 65 years with body mass index ≥ 24 and < 30 kg/m2, (n = 70)	RCT (Parallel)	Significant reduction in abdominal fat area (visceral, subcutaneous, & total fat), and triglyceride levels	Short duration; as such, the potential long-term effects of extract ingestion remain unknown.	Yoshino, 2018 ²³
Rhizome	PMF purified from K. parviflora in capsules	Oral, 12 mg, OD, 12 weeks	Overweight subjects with BMI between 23→30 kg/m2), 20–64 years (n = 80)	RCT (Parallel)	Reduced visceral, subcutaneous, and total fat area	Only Japanese adults included	Yoshino, 2021 ²⁴
	C. Aging-physical & physiological function
Unclear	K. parviflora extract capsules (details of formulation unclear)	Oral, 50 mg, single dose, duration not mentioned	Healthy adults aged 20-29 (n = 12)	RCT (Crossover)	Increased oxygen consumption and decreased respiratory quotient during exercise	Small sample size	Yoshino, 2015 ²⁵
Rhizome	Standardized crude extract of K. parviflora capsules (containing DMF 2.1%, TMF 3.1%, and PMF 2.3%)	Oral, 90 mg, OD, 8 weeks	Healthy elderly subjects, 60 years and older (n = 45)	RCT (Parallel)	Enhanced performance in the 30-s chair stand test and 6-min walk test; Demonstrated antioxidant activity	Small sample size	Wattanathorn, 2012 ²⁶
Rhizome	Dried K. parviflora powder in capsules	Oral, 1.35 g, single dose	Healthy volunteers, mean age 19-21 years (n = 31)	RCT (Crossover)	No acute improvement in repeated sprint, endurance exercise, and time-to-exhaustion test	Body processes that are different between elderly and normally healthy, which would explain selective ergogenic effects	Wasuntarawat, 2010 ²⁷
Rhizome	K. parviflora extract capsules (containing DMF 2.1%, TMF 3.1%, & PMF 2.3%)	Oral, 180 mg, OD, 12 weeks	Soccer players, 15-18 years (n = 60)	RCT (Parallel)	Increased right and left-hand grip strength	Small sample size	Promthep, 2015 ²⁸
Rhizome	K. parviflora extract capsules (details of formulation unclear)	Oral, 360 mg, OD, 12 weeks	Adolescent sport school male students, 15-18 years (n = 194)	RCT (Parallel)	Increased the right-hand grip strength, back-leg strength, and VO2 max; Decreased the time used for 50-meter sprint test	Number of subjects in each sport specialty is not equal with very small numbers in some sport types; longer than 3 months duration of study needed	Sripanidkulchai 2022 ²⁹
	D. Male reproductive system
Unclear	Unclear	Unclear	Healthy males, 50-70 years (n = 13)	Open labeled, single-arm interventio-nal trial	Improved IIEF questionnaire scores (total score, erectile function, intercourse satisfaction, and orgasmic function domain)	Small sample size	Hirsh, 2017 ³⁰
Rhizome	KaempMax ^™- ethanolic K. parviflora rhizome extract capsules (standardized to 5% DMF) in capsules	Oral, 100 mg, OD, 30 days	Healthy men with self-reported mild erectile dysfunction, 50-68 years (n = 14)	Single-arm pilot trial	Improved IIEF questionnaire scores (total score, erectile function, intercourse satisfaction)	Only on healthy men, with mild self-reported erectile function concerns	Stein, 2018 ³¹
	E. Neuropsychiatry
Unclear	K. parviflora extract in capsules (details of formulation unclear)	Oral, 360 mg, OD, 14 days	Healthy volunteers, 24-46 years (n = 80)	RCT (Parallel)	No significant changes in stress scales/index, physiological, and biochemical findings	Short duration of study	Eungpinichpong, 2018 ³²

Preclinical Studies

This review includes 25 animal studies (in vivo), almost all of which employed rodents as the study model (one study used healthy pigs as a model). A majority of the studies (n = 23) investigated rhizome as a standardized extract or in crude form. In terms of route of administration, K. parviflora was given orally in most studies (n = 21), followed by the intravenous (n = 2), and topical route (n = 1). K. parviflora was given for 25 min (single dose study) to 13 weeks, depending on the disease model studied. The characteristics of included animal studies and key findings on efficacy are summarized in in Table 2.

Table 2.

Details of in Vivo Studies of K. parviflora.

Plant part	Test sample	Route, dose, frequency, duration	Studied model	Possible mechanism of action	Summary of efficacy findings	Author, Year
A. Antioxidant
Rhizome	Freeze dried aqueous extract	Topical, applied to the dorsal skin of mice, 50 & 100 mg/kg, 1 h	Female SKH-1 hairless mice	Regulating the intracellular level of oxidative stress.	Phosphorylation of all MAPKs was downregulated in the presence of K. parviflora extract treatment	Lee, 2018 ³³
B. Anti-inflammatory
Rhizome	Ethyl acetate extract, dried powder	Topical (dermal), 50 & 100 mg/kg, 1 h	Female SKH-1 hairless mice	Transcriptional regulation of COX-2	Anti-inflammatory in UV light with sUV -induced PGE2 production via reduction in COX-2 expression	Lee, 2018 ³³
Rhizome	Ethanolic extract	Oral, 150 and 300 mg/kg, OD, 28 days	CFA-induced rat arthritis model	Suppression of the phosphorylation of some proteins, which involves the NF-κB and MAPK pathways.	Significant reduction of arthritis severity scores with combination treatment (extract + indomethacin) compared to indomethacin alone	Ongchai, 2021 ³⁴
C. Antiobesity
Root	50% KPEE, PMFE, or PMF-poor extract diet	Oral, basic feed containing 1% K. parviflora extract, 12 weeks	TSOD mice	Prevent UVB-induced fragility of the obese skin	KPEE and PMFE significantly decreased body weight and suppressed the increase in the thickness of the subcutaneous fat layer; KPEE preserved the stereo structure of the collagenous fibers in the dermis. KPEE was better than PMF in attenuating obesity-induced dermatopathy	Hidaka, 2017 ³⁵
Rhizome	Ethanolic extract	Oral, feed containing 0.5% and 1.0% K. parviflora extract, 7 weeks	C57BL6J male mice fed with high-fat diet	Promotes energy metabolism by activation of BAT with a dose-dependent increase in UCP-1 expression.	Reduced body weight gain, intra-abdominal fat accumulation, and plasma triglyceride & leptin levels;	Yoshino, 2014 ³⁶
Rhizome	EtOAc extract	Oral, pulverized basic feed containing 0.3% and 1.0% K. parviflora extract, daily, 8 weeks	TSOD mice	Activates UCP-1, an essential molecule for metabolic Thermogenes-is	Enhanced the thermogenesis effect of brown adipocytes; Promoted the differentiation of BAT cells, in a dose-dependent manner; Suppressed body weight gain and fat accumulation; Lowered blood lipid and insulin levels; Suppressed the whitening of brown adipose tissue in interscapular adipocytes	Kobayashi, 2016 ³⁷
Rhizome	Crude extract powder Ethanol extract	Oral, 500 mg/kg, OD, 8 weeks Oral, 100 mg/kg, OD, 8 weeks	Male diabetic Nagoya-Shibata-Yasuda mice	Affecting PPARγ ligand-binding capacity and enhancing PPARγ and C/EBP expression.	Suppressed fat accumulation in adipose tissues, liver, and muscles; Reduced plasma glucose and prevented obesity	Ochiai, 2019 ³⁸
D. Antidiabetic
Rhizome	DMF	Oral, 50, 100 and 150 mg/kg, OD, 28 days	Streptozotocin-induced diabetic male adult Wistar rats	6-hydroxyl group of baicalein (56,7-trihydroxyflavone) was important to α-glucosidase inhibitory activity	Decreased serum glucose and triglycerides; Increased serum insulin	Moon, 2016 ³⁹
Rhizome	PMF	Oral, 22 mg/mL,BD, 6 weeks	Middle age male Wistar rats (12-14 months old)	Enhance ment of glucose uptake via the GLUT-4 of the adipose tissue and other GLUT-4-dependent cells	Decreased plasma glucose	Yorsin, 2016 ⁴⁰
E. Cardiovascular effects
Rhizome	Saline extract	IV, 12.5 and 100 mg/kg, 0.5 mL/minute, 30 min	Male Wistar rats	Modulation of excitation–contraction coupling or the indirect effect via its effect on vasculature	IV extract at 100 mg/kg increased cGMP level via downstream cascade from NOS and decreased cardiac function (decreased ejection systolic pressure & ejection systolic volume) in the normal rat's heart	Weerateerangkul, 2012 ⁴¹
Rhizome	Saline extract	IV, 100, 50, 25, 12.5 mg/kg, 2 mL/min, 25 min	Healthy pigs	Effect on NO-cGMP signaling which has a role in various ionic regulations of cardiomyocy-te	Ventricular fibrillation induction and defibrillation study: IV extract (50 and 100 mg/kg) increased the defibrillation threshold, upper limit of vulnerability, and the diastolic pacing threshold. Extract also decreased systolic blood pressure, diastolic blood pressure, and mean arterial pressure	Weerateerangkul, 2013 ⁴²
Rhizome	PMF	Oral, 22 mg/kg, BD, 6 weeks	Middle age male Wistar rats (12-14 months old)	Not mentioned	No changes in vascular smooth muscle function in aorta or mesentery; Upregulated the expression of blood vessel eNOS and CSE proteins, increased NO and H2S productions to modulate the blood vessel function by opposing contraction to phenylephrine and enhancing vasodilatation to acetylcholine; Decreased plasma glucose and increased plasma HDL cholesterol levels.	Yorsin, 2016 ⁴⁰
Rhizome	Dichloromethane extract	Oral, 100 mg/kg, OD or BD, 6 weeks	Male Wistar rats	Increase in nitric oxide production from the vascular endothelium to attenuate the vasocontraction and potentiated the vasorelaxation to acetylcholine.	In middle-aged rats: Increased NO production by increasing the eNOS protein in blood vessels which resulted in a decrease of the maximal contractile response to phenylephrine and an increase of the dilatation of blood vessels to acetylcholine.	Yorsin, 2014 ⁴³
F. Aging-physical & physiological function
Rhizome	Standardized 95% ethanolic extract containing 14.1% (w/w) DMF	Oral, 200 mg/kg, OD, 10 weeks	Normal diet mice and high-fat diet obese mice	Mitochondrial biogenesis and the SIRT1/AMPK/PGC-1a/PPARδ signaling pathways	Enhanced running endurance and increased the skeletal muscle weight/body weight ratio	Kim, 2018 ⁴⁴
Rhizome	Crude hexane extract, chloroform crude extract, and methanol crude extract	Oral, 500 mg/kg, OD, 25 days	Adult male Swiss albino mice	Not mentioned	Demonstrated adaptogenic properties via shorter mouse immobilization time	Pripdeevech, 2012 ⁴⁵
Rhizome	70% methanolic extract	Oral, 200 mg/kg and 500 mg/kg, OD, 7 days	Male Std-Wistar/ST rats, LPS-induced DIC rat	Not mentioned	Reduced blood passage time and improved blood fluidity; PMF is the most dominant methoxyflavone in terms of fibrinolysis activation.	Murata, 2013 ⁴⁶
Rhizome	0.1% HMF derivative mixture from methanolic extract	Dose unclear, 4 weeks	Middle-aged male SAMP1 mice	Activates mTOR signaling	Induced myotube hypertrophy and promoted protein synthesis in myotubes; Increased myofiber size in the soleus muscle.	Ono, 2019 ⁴⁷
Rhizome	Aqueous extract	Oral, 45 mg/kg, OD, 4 weeks	Male ddY mice	Activation of AMPK similar to agonist drug 5-aminoimidazole-4-carboxyamide ribonucleotide	Increased physical fitness performance and muscular endurance (forced swimming, open-field, inclined plane, and wire-hanging test)	Toda, 2016 ¹⁹
Rhizome	Ground 2.5% K. parviflora	Oral, 4 g/kg, OD, 2 weeks	C57BL/6J mice	Modulate the peripheral clock in the liver or other organs, synchronize SCN or extra-SCN oscillators in the brain via hormonal signals or neural connection	More rapidly entrained the locomotor activity rhythms compared to control group	Yoshida, 2020 ⁴⁸
G. Male reproductive system
Rhizome	1% Aqueous suspension of methanolic extract	Oral, 140, 280, and 420 mg/kg, OD, 6 weeks	Male Wistar rats	Improvement of gene markers miRNAs, miR-328, miR19b, and miR-34	Increased serum testosterone levels and epididymal sperm parameters	Al- Rawaf, 2021 ⁴⁹
Rhizome	95% Ethanolic extract	Oral, 70 mg/kg, OD, 4 weeks	Healthy rats	Enhance NO production in MPOA but further studies needed	Extract alone did not improve sexual indicators. In combination with exercise, the extract improved parameters such as weights of epididymis, seminal vesicles, prostate gland, and levator ani muscle	Chaturapanich, 2012 ⁵⁰
Rhizome	Dried powder of K. parviflora extract in distilled water & Tween 80, 1% suspension	Oral, 140, 280 and 420 mg/kg, OD, 6 weeks	STZ-induced diabetic male rats	Increasing blood flow to the testis, enhancing NO production MPOA	Enhanced serum testosterone levels, increased testicular weight & sperm density, and improved sexual performance	Lert-Amornpat, 2017 ⁵¹
H. Skin health
Rhizome	Ethanol extract	Oral, 200 mg/kg, OD, 24 weeks	Hairless Mice	Inhibition of cellular senescence & mitochondria-l dysfunction.	Inhibited wrinkle formation, skin atrophy, and loss of elasticity by increasing the collagen and elastic fibers	Park, 2017 ⁵²
Rhizome	Ethanol extract	Oral,100 or 200 mg/kg, OD, 13 weeks	UVB-induced photoaging, involve irradiated hairless mice	Inhibition of MMP responsible for photoaging	Prevented wrinkle formation & the loss of collagen fibers and reduced UVB-induced expression of MMP-2, MMP-3, MMP-9, & MMP-13 via the suppression of c-Jun and c-Fos (protooncogene) activity	Park, 2014 ⁵³
I. Urology
Rhizome	Ethanol extract, powdered	Oral, 100, 200 and 500 μg/mL, 7 days	Male Crj: CD Sprague-Dawley rats (BPH model species)	Inhibited activity against 5α-reductase	Suppressed the weights of prostates and seminal vesicles in BPH	Murata, 2013 ⁵⁴
J. Immunomodulation
Rhizome	Ethanolic extracts	Oral, 200 mg/kg, OD, 19 days	Swiss albino mice	Not mentioned	Improved titer counts for humoral immune response and lymphocyte count	Devi, 2020 ⁵⁵
K. Neuropsychiatry applications
Rhizome	Ethanol extract;	Oral, 100 mg/kg, OD, 21 days	Male Sprague Dawley rats	Stimulate neurogenesis by increasing survival of newborn neurons and proliferating NPCs	Improved spatial memory deficits and prevented the reduction of proliferating cells caused by valproic acid; increased doublecortin protein levels within the hippocampus	Welbat, 2016 ⁵⁶
L. Arthritis
Not mentioned	DMF and TMF, extracted from K. parviflora	Oral, 100 mg/kg, OD, 7 days	Monoiodoacetic acid induced-osteoarthritis rat	Reduction of matrix metalloproteinases’ (MMPs) expression which are the main enzymes that degrade cartillagenous collagen	Reduced the expression of metalloproteinas-es and improved pain threshold & severity of osteoarthritic cartilage lesions	Kobayashi, 2018 ⁵⁷

In vitro studies (n = 57) investigated 15 different potential biological effects of K. parviflora. Of these, anti-cancer (n = 11) and antiaging (n = 8) effects were most researched. Like clinical and animal in vivo studies, the rhizome of this herb was the most investigated plant part in in vitro studies (n = 48). As for formulation, more than half (n = 36) investigated standardized extracts of K. parviflora. Seventeen studies used specific compounds either extracted from the plant or commercially bought. Four studies used both the extract and compound. The characteristics of included in vitro studies and key findings on efficacy are summarized in Table 3.

Table 3.

Details of in vitro studies of K. parviflora.

Plant part	Test sample	Test concentration	Studied model	Summary of efficacy findings	Author, Year
A. Antioxidant
Rhizome	Unclear	12.5–400 μg/mL	JB6 P + and HaCaT cells	Exhibited ABTS and DPPHradical scavenging activity in dose-dependent manner	Lee, 2018 (33)
Rhizome	1% Aqueous suspension of methanolic extract	100–500 μg/mL	DPPH, NBT, FRAP assay	Demonstrated antioxidant activity	Al-Rawaf, 2021 (49)
Rhizome	50% Aqueous ethanolic extract	250, 500 and 1000 μg/mL	Human umbilical vein endothelial cells	Demonstrated antioxidant activity; reduced ROS production	Horigome, 2017 (58)
Leaf	Methanolic extract	1 mg/mL	ABTS, DPPH, CUPRAC, FRAP, MCA, PBD	Demonstrated free radical scavenging and antioxidant activity	Park, 2021 (59)
B. Anti-inflammatory
Rhizome	Ethanolic extract	10–25 μg/mL	Cartilage explant culture model	Chondroprotective potential: suppressed sulfated glycosaminoglycans were released while preserving high accumulation of proteoglycans, suppressed NF-κB and MAPK signaling pathways	Ongchai, 2021 (34)
Rhizome	DMF & TMF	25 and 50 pg/mL	RBL-2H3 cells stimulated with an IgE antigen or a calcium ionophore	Inhibited antigen-induced degranulation	Horigome, 2014 (10)
Rhizome	50% aqueous ethanolic extractDMF	250, 500 and 1000 μg/mL5, 25, 50 μg/mL	Monocyte adhesion assay	Both extract and DMF reduced nitrite levels, nitric oxide synthase expression, THP-1 cell adhesion, inflammatory mediators, and endothelial function-related genes	Horigome, 2017 (58)
Rhizome	95% Ethanolic extract	250 and 500 μg/mL	Lipopolysaccharide-stimulated murine macrophage-like cell line	Down-regulated the expression of iNOS, COX-2, and TNF-α levels	Jin, 2018 (60)
Rhizome	Ethanolic extract	3 to 30 μg/mL	SW982, human synovial sarcoma cells (activated using a combination of IL-1β and IL-17A cytokines)	Showed antiarthritic and anti-inflammatory properties: Suppressed the expression of TNF-α and IL-1β, down-regulated the expression of COX2, PGE2, and NO,suppressed cytokines-induced p38/STAT1 and STAT3 pathways, reduced mRNA expression of cadherin-11, and inhibited cell migration, andinhibited the phosphorylation of p38 MAPK, STAT1 cascade & STAT3 signaling pathway	Kongdang, 2019 (61)
Rhizome	Crude ethyl acetate extract, dried powdered	8–128 μg/mL	AGS (gastric adenocarcinoma cells)	Anti-inflammatoryActivity: Downregulated both IL-8 expression and its further inflammatory mechanism in neutrophil chemotaxis, monocyte activity, and sHP-mediated monocyte chemotaxis	Nemidkana, 2020 (62)
C. Antiobesity
Rhizome	EtOAc extract	1, 3, 10, and 30 μg/mL	Primary brown preadipocytes of 3-week-old male ICR mice	Enhanced energy consumption by upregulating mRNA expression levels of PPARγ, UCP-1, and β3AR	Kobayashi, 2016 (37)
Rhizome	Ethyl acetate extract	3–100 μg/mL	3T3-L1 murine preadipocytes	Enhanced lipolysis, suppressed hypertrophy,& suppressed lipid accumulation	Okabe, 2014 [(8)]
Rhizome	Ethyl acetate extract and polymethoxyflavonoids	1 and 3μg/mL	3T3-L1 Preadipocytes differentiation into adipocytes	Induced differentiation of 3T3-L1 preadipocytes to adipocytes, adiponectin mRNA levels, and release of adiponectin; Enhanced the expression of PPARγ	Horikawa, 2012 (63)
Rhizome	Ethyl acetate extract, powdered	3–100 μg/mL	3T3-L1 murine preadipocytes	Decreased intracellular triglycerides,upregulated mRNA expression of adiponectin, ATGL, & HSL and suppressed hypertrophy in mature adipocytes	Okabe, 2014 (8)
Rhizome	Tetramethylkaempferol,Pentamethylquercetin, 3,7,4’-trimethylkaempferol isolate	1–30 μM	3T3-L1 cellspre-adipocyte cells	Enhanced accumulation of triglyceride; Promoted adipogenesis of 3T3-L1 cells	Matsuda, 2014 (64)
D. Cardiovascular effects
Rhizome	Saline extract	75, 150, or300 μg/mL.	Rat ventricular myocytes	300 μg/mL significantly decreased the Ca²⁺ transient amplitude, rising and decay rate within 5 minutes and showed the progressive decrease of these parameters at 10 minutes;L-NAME increased cardiac function without the changing of Ca²⁺ transient	Weerateerangkul, 2012 (41)
E. Aging-physical & physiological function
Rhizome	0.1% HMF derivative mixture from methanolic extract	5 μg/mL	Murine myoblast C2C12 cells	Promoted protein synthesis requiring intracellular Ca²⁺, and not extra-cellular Ca²⁺	Ono, 2019 (47)
Rhizome	Aqueous extract	10 μg/mL	Mouse soleus muscle C2C12	Downregulated mRNA expression of IL-6 and TNF-α in soleus muscle	Toda, 2016 (19)
Rhizome	Ethanolic extract	10 μg/mL	Immortalized mouse myoblast cell line (C2C12 cells)	Increased uptake of 2-deoxyglucose, lactic acid and mRNA expression of GLUT4 and MCT1 in myoblast cell, increased expression of AMPK and PGC-1a, and increased production of ATP & mitochondrial biogenesis	Toda, 2016 (19)
Rhizome	KPEE	0.005–0.5 mg/mL	Immortalized embryonic fibroblasts cells (NIH3T3 cells)	Induced Per2, Cry1, and Bmal1 expression which modulates circadian rhythms in a concentration-dependent manner; lengthened the circadian period of Per2-GLuc expression, enhanced the amplitude of circadian rhythms, lengthened the circadian period and delayed the phase of circadian rhythms	Yoshida, 2020 (48)
Rhizome	80% ethanol extract,powdered; TMF, PMF	2, 10, 20, 100 μg/mL	Human SIRT1 enzyme (SE-239)	Increased SIRT1 catalytic activity and anti-glycation activity	Nakata, 2014 (65)
Rhizome	MRR extractedfrom the rhizomes of K. parviflora.	5–30 μg/mL	PC12D pheochromocytoma cells	Promoted cAMP response element CRE-mediated transcription	Natsume, 2020 (66)
Rhizome	Methanol extract; PMF, DMF, TMF	10, 20, 40 μM	PC12 cell line for Alzheimer's disease	Exhibited AChE inhibitory activity	Seo, 2017 (67)
Leaf	Methanolic extract	1 mg/mL	AChE, amylase, and BChE, and tyrosinase inhibitory assays	Inhibitory activity in AChE, amylase, and BChE and tyrosinase inhibitory assays	Park 2021 (59)
F. Male reproductive system
Rhizome	50% Aqueous ethanolic extract	0, 0.5, 1.0, 2.5, 5.0, 10.0 μg/mL	Testosterone production	Enhanced testosterone production via cyclic AMP (cAMP)/cAMP response, element binding & protein signaling	Horigome, 2016 (68)
Rhizome	PMF	0.01–3 mM	Relaxant mechanisms on isolatedhuman cavernosum	Induced relaxation of phenylephrine precontracted human corpus cavernosum strips through voltage dependent Ca²⁺ channels and other mechanisms associated with calcium mobilization	Jansakul, 2012 (13)
G. Skin Health
Rhizome	Ethanol extract	0-10 μg/mL	Human dermal fibroblasts	Increased cell growth and suppressed senescence-associated β-galactosidase activation, inhibited the expression of cell-cycle inhibitors, stimulated the expression of cell-cycle activators, attenuated inflammatory mediators, and increased mRNA expression of genes modulating mitochondrial biogenesis and function	Park, 2017 (52)
Rhizome	80% Methanol extract, TMF	0-100 μM	NHDFs	Inhibited ROS production, reduced the secretion of MMP-1 induced by TNF- α, suppressed extracellular matrix degradation & the expression of pro-inflammatory cytokines IL-1, IL-6, and IL-8, suppressed the excessive increase in AKT, and COX-2, and increased heme oxygenase -1 expression	Lee, 2022 (69)
Rhizome	95% KPEE	0, 5, 10, or 20 μg/mL	Acne (human keratinocyte HaCaT cells)	Inhibited the lipogenesis of sebocytes and modulated the expression of iNOS and NF-κB signal molecules in P. acnes-stimulated HaCaT cells	Jin, 2018 (60)
Rhizome	PMF	3 μg/mL	Primary human dermal fibroblasts	Suppressed cellular senescence, reactive oxygen species, and the senescence-associated secretory phenotype in primary human dermal fibroblast; increased tropocollagen synthesis and alleviated free radical-induced cellular and mitochondrial damage	Klinngam, 2022 (70)
Rhizome	Methanol extract, powdered	0–10 μg/mL	B16 melanoma 4A5 cells	Inhibited melanogenesis and mRNA expressions for tyrosinase, TRP-1, and TRP-2	Ninomiya, 2016 (71)
Rhizome	TMF	0–100 μM	Human dermal fibroblasts stimulated by TNF-α	Inhibited MMP-1 production and stimulated COLIA1 expression; Suppressed TNF-α-stimulated generation of ROS and proinflammatory mediators; Inhibited the pathways regulating fibroblast damage MAPK, NF-κB, AP-1	Phung, 2021 (72)
Rhizome	KPEE	0–1000 μg/mL	LPS-induced RAW264.7 cells	Reduced inflammatory and psoriatic markers including iNOS, COX-2, TNF-α, IL-1, IL-6, IL-17, IL-22, and IL-23; Decreased cell migration and proliferation	Takuathung, 2021 (73)
H. Urology
Rhizome	PMF	Unclear	Assay for 5α-reductase inhibitory activity	PMF was found to be the most potent inhibitor of steroid 5α-reductase with the IC₅₀ of 20 µM	Kim, 2013 (74)
I. Anticancer
Rhizome	TeMF, TMF,and 5-hydroxy-TeMF	0-500 μM	Human colorectal cancer cells(HCT-15)	Inhibited HCT-15 cells in a dose-dependent manner.TMF produces a higher level of fragmented DNA compared to TeMF and 5-HTeMF, and showed the highest levels of caspase-3 activity	Hossain, 2012 (75)
Not reported	Tectochrysin	6.25, 12.5 and 25 μM	LPS-primed macrophages	Inhibited ERK1/2 phosphorylation, sequentially suppressed downstream iNOS, TNF-α& IL-6 transcription, and inhibited NO, TNF-α, & IL-6	Hou, 2018 (76)
Unclear	Krachaidum tea and isolated DMF, TMF, & PMF	200 and 400 μg/mL	Human gastric cell lines (SNU-16)	TMF inhibited the proliferation of SNU-16 human gastric cancer cells in a concentrationdependent manner and induced apoptosis via endoplasmic reticulum stress	Kim, 2018 (77)
Unclear	Anthocyanidins enriched extracts	0, 20, 50, 100, 200, and 300 mg/mL	Ovarian cancer cells (ES-2, OV-90)	Decreased ES-2 and OV-90 cell proliferation, increased late apoptosis with cell cycle arrest at sub G0/G1 phase, and hampered mitochondrial membrane permeability	Kim, 2022 (78)
Rhizome	95% Ethanolic extract	0–100 μg/mL	Ovarian clear cell carcinoma	Inhibited IL-6 & MCP-1 production at transcription andtranslation levels via the suppression of NF-κB signal transduction, increased expression of IκB protein, inhibited IL-6 & MCP-1 production from THP-1 activated by LPS, reduced the migration of THP-1, decreased ERK1/2 and AKT phosphorylation, andinduced MCL-1 expression	Thaklaewphan, 2021 (79)
Rhizome	95% ethanolic extract	0 - 10 mg/mL	Ovarian cancer cell line SKOV3	Cytotoxic to SKOV3 cells with increasing concentration;high concentrations induced SKOV3 cell apoptosis, and suppressed cell proliferation, cell migration & invasion	Paramee, 2018 (80)
Rhizome	95% ethanolic extract	0.01- 1 mg/mL	Cervical cancer cells (HeLa cells)	Reduced HeLa cell viability with a dose-dependent cytotoxicity activity through induction of apoptotic cell death	Potikanond, 2017 (81)
Rhizome	100% dichloromethane extract	2.5 and 5 μg/mL	PANC-1 under the conditions of NDM and DMEM	PMF displayed the most potent activity with a PC50 value of 0.8 µM	Sun, 2021 (82)
Rhizome	Ethanolic extract	7.5 and 15 μg/mL	HPV18-positive cervical cancer cell line, HeLa	Suppression of the cellular expression and secretion of IL-6 protein and STAT3 activation in HeLa cells induced by epidermal growth factor; Inhibited autocrine IL-6 signaling	Suradej, 2019 (83)
Rhizome	Ethanolic and water extract	Unclear	Human urinary bladder cancer cell, T24) and normal cell lines (HUVEC)	Ethanol extracts induced cell death in T24 via p53 gene expression and prolonged cell survival in HUVEC through SIRT1 gene expression	Tangjitjaroenkun, 2021 (84)
Rhizome	Supercritical CO2 & ethanolic extract	25 & 50 μg/mL	Human cervical cancer HeLa and human gastric adenocarcinoma AGS cell line	Supercritical CO2 extract showed more potent antiproliferative activity than the ethanol extract against both cell lines due to a higher concentration of PMF	Wongsrikaew, 2012 (85)
J. Immunomodulation
Rhizome	Dichloromethane (CH2Cl2) extract andEtOAc-soluble fraction of K. parviflora extract5-Hydroxy-3,7,4′-TMF5,3′-dihydroxy-3,7,4′-TMF	0–1000 μg/mL	Antigen-mediated degranulation of RBL-2H3 cells	Anti-allergenic activity (type 1) by suppression of FcεRI levels in the plasma membrane	Kobayashi, 2015 (86)
K. Antimicrobial
Unclear	Ethanolic extract	1–100 μg/mL	Human foreskin fibroblasts	Anti-Plasmodium (Plasmodium falciparum)Anti-Toxoplasma (Toxoplasma gondii)IC₅₀ value:P. falciparum: 28.7 µg/mLT. gondii: 53.5 µg/mL	Leesombun, 2019 (87)
Rhizome	Ethyl acetate extract, dried powdered	8–128 μg/mL	AGS, gastric adenocarcinoma cells	At 32 μg/mL, extract has a growth-inhibitory effect against H. Pylori;Inhibited caspase-dependent apoptosis stimulated by H. Pylori infection	Nemidkana, 2020 (62)
Root	Crude water and ethanolic extracts	2.2 g/mL & 438.4 g/mL	MDCK cells	Significantly inhibited H5N1 virus replication in MDCK cells when compared to the control group, showing antiviral activity	Sornpet, 2017 (88)
Not applicable	Compound structures obtained from zinc database	Unclear	Molecular docking of tyrosine aminotransferase of Leishmania donovani	DMF or chrysin dimethyl ether exhibited stable geometrical properties and further trajectory analysis revealed the high-affinity interactions with active site residues	Sasidharan, 2020 (89)
L. Hepatoprotection
Rhizome	Kaempferiaosides A and B	0-100 μM	Primary cultured mouse hepatocytes	Showed higher hepatoprotective activity than silymarin (control)	Chaipech, 2012 (90)
M. Ophthalmology
Rhizome	Isolated polymethoxylated flavonesfrom K. parviflora extract	64 μM	SRA01/04, Human lens epithelial cells	PMF (DMF, the most potent inhibition) of extract inhibited phorbol ester- induced MMP-9 activity and the mRNA expression through the suppression of MAPKs phosphorylation in human lens epithelial cells	Miyata, 2019 (91)
N. Arthritis
Not mentioned	DMF and TMF, extracted from K. parviflora	Oral, 100 mg/kg, OD, 7 days	Monoiodoacetic acid induced-osteoarthritis rat	Reduced the expression of metalloproteinases and improved pain threshold & severity of osteoarthritic cartilage lesions	Kobayashi, 2018 (57)
Rhizome	Ethanolic extract	3–30 μg/mL	SW982, human synovial sarcoma cells- (activated using a combination of IL-1β and IL-17A cytokines)	Suppressed the expression of TNF-α & IL-1β;down-regulated the expression of COX2, PGE2, NO;suppressed cytokines-induced p38/STAT1 & STAT3 pathways;reduced the mRNA expression of cadherin-11 and inhibited cell migration;inhibited the phosphorylation of p38 MAPK, STAT1 cascade and STAT3 signaling pathway	Kongdang, 2019 (61)
O. Others
Rhizome	5-hydroxy-DMF	1-1000 μM	High-throughput drug screening assay for inhibitors of Ca²⁺-signaling	Potent inhibitory activity against the Ca²⁺ mediated cell-cycle regulation	Boonkerd, 2014 (92)
Rhizome	Dichloromethane extract	50 & 100 μM	sEH inhibitory activity assay	5 Compounds isolated from flavonoid derivatives are shown to be potent sEH inhibitors; sEH increases the levels of EETs and reduce those of DHETs,which might have therapeutic implications in multiplediseases	Thao, 2016 (93)
Rhizome	PMF	50 & 100 μM	Human Intestinal Caco-2 Cells	Enhanced intestinal TJ barrier integrity;increased the cytoskeletal association and cellular expression of the TJ proteins, zonula occludens-1, claudin-3, and claudin-4;increased transepithelial electrical resistance;decreases permeability to fluorescein-conjugated dextran	Mayangsari, 2021 (94)

DPPH: 2,2-diphenyl-1-picrylhydrazyl; CUPRAC: cupric reducing antioxidant capacity; FRAP: ferric reducing antioxidant power; NBT: Nitroblue Tetrazolium; MCA: metal chelating ability; PBD: phosphomolybdenum; ABTS: 2,2-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid); AChE: acetylcholinesterase; BChE: butyrylcholinesterase; RCT: randomized controlled trial; PGE2: prostaglandin E2; COX-2: cyclooxygenase-2; CFA: Complete Freund’s adjuvant; NF-κB: Nuclear Factor-kappa B; MAPK: mitogen-activated protein kinase; RBL-2H3: rat basophilic leukemia; DMF: 5,7-dimethoxyflavone; TMF: 5,7,4′-trimethoxyflavone; THP-1: human leukemia monocytic cell line; iNOS: inducible nitric oxide synthase; TNF-α: tumor necrosis factor alpha; IL: interleukin; NO: nitric oxide; NOS: nitric oxide synthase; P38: p38 mitogen-activated protein kinase; STAT: signal transducer and activator of transcription; AGS: adenocarcinoma gastric cell line; sHP: Src homology 2 domain-containing phosphatase; TeMF: 3,5,7,4 tetramethoxyflavone; BAT: activated brown adipose tissue; PMF: 3,5,7,3′,4′-pentamethoxyflavone; BMI: body mass index; KPEE: ethanolic extract of K. parviflora; PMFE: PMF-rich extract; EtOAc: ethyl acetate; TSOD: Tsumura Suzuki, Obese Diabetic; PPARγ: peroxisome proliferator- activated receptor gamma; UCP-1: uncoupling protein 1; β3AR: β-3 adrenergic receptors; ATGL: adipose triglyceride lipase; HSL: hormone-sensitive lipase; IV: intravenous; cGMP: cyclic guanosine 3’,5'-cyclic monophosphate (cGMP); L-NAME: L-N^G-nitroarginine methyl ester; eNOS: endothelial nitric oxide synthase; CSE: cystathionine-γ-lyase; H₂S: hydrogen sulphide; HDL: high density lipoprotein; ROS: reactive oxygen species; TJ: tight junction; sUV: solar wavelengths; VO₂ max: maximal oxygen consumption; SIRT1: sirtuin-1/5’; AMPK: adenosine monophosphate-activated protein kinase; PGC-1a: peroxisome proliferator-activated receptor-gamma coactivator -1 alpha; PPARδ: peroxisome proliferator-activated receptor delta; LPS: lipopolysaccharide; DIC: disseminated intravascular coagulation; HMF: 5-hydroxy-7-methoxyflavone; SAMP1: senescence-accelerated mouse-prone 1; GLUT4: glucose transporter 4; MCT: monocarboxylate transporter 1; ATP: adenosine triphosphate; MRR: methoxyflavones-rich residue; CRE: cAMP response element; IIEF: International Index of Erectile Function; STZ: streptozotocin; UVB: ultraviolet B; MMP: matrix metalloproteinases; NHDFs: normal human dermal fibroblasts; HaCat: Human Adult Low Calcium High Temperature; TRP: tyrosine-related protein; COLIA1: collagen type I alpha 1; AP-1: activator protein 1; BPH: benign prostatic hyperplasia; ERK1/2: extracellular signal-regulated protein kinase 1 and 2; MEK: mitogen-activated protein kinase; MCP-1: monocyte chemoattractant protein-1; IκB: inhibitor kappa B; AKT: Protein kinase B; MCL-1: myeloid leukemia cell differentiation protein; PANC-1: human pancreatic cancer cell line; NDM: nutrient-deprived medium; DMEM: nutrient-rich medium; HPV: human papillomavirus; sEH: soluble epoxide hydrolase; EETs: epoxyeicosatrienoic acids; DHETs: hydroxyeicosatetraenoic acids; HUVEC: Human umbilical vein endothelial cell; FcεRI: high-affinity IgE receptor; MDCK: Madin–Darby canine kidney; IFN: interferon; C/EBP: CCAAT/enhancer-binding protein; mTOR: mechanistic target of rapamycin complex 1; SCN: suprachiasmatic nucleus; MPOA: medial pre-optic area of the hypothalamus; NPC: neural progenitor cells

Discussion

This review of current evidence shows that K. parviflora is a plant with potential for 16 different diseases and other various pharmacological applications, with the rhizome most popularly used traditionally and investigated, and PMF as the most studied bioactive phytoconstituent. A few effects were only demonstrated at the in vitro stage, including anticancer, antimicrobial, hepatoprotective effects, and potential benefits in ophthalmological diseases. Effects such as antioxidant, antidiabetic, cardiovascular, skin health, urology and immunomodulation have shown positive findings in preclinical studies only, at both in vivo and in vitro levels, thus needing further validation in clinical studies. K. parviflora shows conflicting findings in neuropsychiatry applications whereby an in vivo animal study demonstrated its ability to ameliorate cognitive impairments while no significant effect was observed in healthy adults in terms of changes in physical or psychological stress. Positive findings were consistently seen for anti-inflammatory and anti-obesity across the preclinical and clinical studies. Beneficial effects were also observed similarly via improvements in aging-physical and physiological functions and in the male reproductive system. Details of these general trends of research landscape and research gaps is in Supporting information: Supplemental Table S1. A recent meta-analysis which included 57 articles (both clinical and preclinical studies included) focusing on metabolic syndrome and erectile dysfunction suggested improvements in blood glucose, physical, and exercise performance, but not other metabolic or reproductive function parameters, following K. parviflora administration.⁹⁵ The variation in effects could be due to high heterogeneity of intervention including formulation, dose, duration, and study population.

A meaningful research approach for K. parviflora would be focusing on the potentially bioactive compounds. Based on published studies included in this review, the rhizome extracts of K. parviflora that have been explored include those from ethyl acetate, methanolic, ethanol, saline, aqueous, and dichloromethane. From these extracts, the phytochemical compounds of K. parviflora that have been studied include flavonoids (such as tetramethylkaempferol, tectochrysin, anthocyanidins, kaempferiaosides A and B, pentamethylquercetin, and trimethylkaempferol) and methoxyflavones (such as DMF, TMF, TeMF, and PMF). Additional phytochemical studies have identified other compounds within K. parviflora including di-O-methylpinocembrin, bisdemethoxycurcumin, aloe-emodin,⁹⁶ phenolic compounds, phenolic glycosides, kaempanosides,⁹⁷ and terpenes⁴⁵ Several researchers have taken the initiative to study the preclinical efficacies of the mentioned compounds,^45,97 but product development or clinical studies related to these compounds are not yet available. Hence, these compounds represent potential areas for further research and product development based on K. parviflora.

Although K. parviflora has been used as a functional food and supplement in various forms for centuries, its safety remains to be ascertained, especially when used on a long-term basis. Sub-chronic toxicity (90 days) study on a standardized hydroalcoholic extract of K. parviflora extract (medium dose at 125 mg/kg body weight/day K. parviflora extract and high dose at 249 mg/kg body weight/day K. parviflora extract) in Sprague-Dawley rats showed no signs of toxicity without any meaningful histopathological changes in the collected organs. No abnormalities with insignificant changes to biochemical and hematological parameters were observed when compared to the control group. Genotoxicity tests using a bacterial reverse mutation assay using five different strains also exhibited no mutations up to 5000 µg/plate.⁹⁸

Another aspect of safety that should be considered is herb-drug interactions. An animal study showed herb-drug interaction between K. parviflora extract and paracetamol by decreasing the concentration of paracetamol through accelerated drug clearance and elimination rate in male Wistar rats for nine days.⁹⁹ K. parviflora extract was also found to interact with sildenafil, a PDE-5 inhibitor in rats. K. parviflora interfered with first-pass metabolism and absorption of sildenafil in the liver and intestine. This effect could be clinically important as K. parviflora has been investigated for use as a male sexual stimulant or reproductive enhancer, while slidenafil is a common drug used for erectile dysfunction.¹⁰⁰ This could be attributed to its inhibitory effect on p-glycoprotein and multidrug resistance-associated proteins, which are efflux ATP-binding cassette transporters in the intestines that affect drug absorption and oral bioavailability.^99,100

Herb-drug interaction studies also showed that K. parviflora extract could affect CYP enzyme activity in rodents. In detail, K. parviflora extract could induce the enzymatic activity of several CYP enzymes, including CYP1A1, CYP1A2, CYP2B, and CYP2E1.¹⁰¹ Studies on DMF of K. parviflora also showed it significantly reduced the expression of CYP3A11 and CYP3A25 in the liver. The CYP enzyme family is responsible for metabolizing many drugs, such as vitamin D3, dexamethasone and herbs, such as berberine.^102–104 Consequently, the use of K. parviflora will eventually increase (when acting as an inhibitor) or decrease (when acting as an inducer) the blood concentration of drugs that are metabolized by CYP enzymes.¹⁰⁵ In addition to harms, herb-drug interactions that increase the bioavailability of the other drugs could potentially be lobbied for benefits instead. For example, K. parviflora extract can increase the oral absorption of certain anticancer drugs (eg paclitaxel), which therefore could be further investigated for its potential to improve the delivery route of the affected drug in a beneficial way (eg, from intravenous injection to oral).¹⁰⁶ Due to the potential interactions, co-administration of K. parviflora with conventional drugs needs to be carefully considered on a case-by-case basis.

Due to concerns for potential raw material sourcing issues, it might be beneficial for local researchers of industry to strategically seek alternative plants which carry the main bioactive phytoconstituents of K. parviflora, ie, the methoxyflavones. For example, DMF can be isolated from the aerial parts of Caesalpinia pulcherrima¹⁰⁷ and rhizomes of Boesenbergia pandurata.¹⁰⁸ Both C. pulcherrima (local name: Bunga Merak) and B. pandurata (local name: Temu Kunci) are plants that were cultivated locally or naturally occurring in Malaysia.¹⁰⁹ Traditionally, C. pulcherrima was used for diarrhea, distended stomach, fever and cough¹¹⁰ while B. pandurata was used for various skin infections, including ringworm, impetigo, and abscesses; relieving joint pains and malarial symptoms.¹¹¹ Another potential local plant which can be further investigated is Orthosiphon aristatus,¹¹² locally known as misai kucing, which has been traditionally used for diuretic activity.¹⁰⁷ PMF extracted from the leaves of O. aristatus has shown anti-infective properties.¹¹⁰

The main strength of this review is that we have covered both published (from several electronic databases) and gray literature, both local and international. This approach enabled the review team to collect a variety of literature to synthesize multi-angled and locally relevant views when considering the research landscape and gap for the local researchers and industries in Malaysia.

Review Limitations

A major limitation of this review is that searches, screening, and data extraction were performed by individual investigators instead of independent pair of researchers with cross-checking, which may have led to missing out on some literature. This review also focuses on efficacy rather than safety, which may warrant a separate review of its own in the future. Some considerations for safety aspects were discussed above. Lastly, due to the nature of narrative scoping reviews and our objective to map research landscape, we did not perform critical appraisal on the quality of included studies. Critical appraisal of study findings can be undertaken in future systematic reviews which focus on more specific outcomes instead.

Conclusions

In conclusion, K. parviflora is a plant with potential for various pharmacological applications, with the rhizome most popularly used and investigated and the PMF as the most studied bioactive phytoconstituent. Further research expanding on its traditional use for men's health could be beneficial. However, local research direction must appraise operational considerations, in particular raw material sourcing and sustainability.

Materials and Methods

This review was designed to provide an overview of the current published and gray literature regarding K. parviflora, including its traditional use and scientific literature on its efficacy and safety. This literature review can be broadly divided into two parts: (1) a review of traditional use; and (2) a review of published biomedical research on biological activities and health effects.

Searches on Traditional use

The search for information on traditional uses of K. parviflora was carried out by reviewing published journals, herbal monographs, books, proceedings, and pharmacopoeia accessible within our institution. Among the references reviewed were the ‘Thai Herbal Pharmacopeia 2018’ and ‘Khazanah Perubatan Melayu - Tumbuhan Ubatan (Volumes 1-3)’.^1,114–116

Published Literature Review

A systematic search was conducted by investigators on electronic databases including MEDLINE, CENTRAL, and Web of Science for relevant articles published in the past 10 years until October 2022. The keywords combination used include “Kaempferia parviflora”, “Kaempferia rubromarginata”, “Stahlianthus rubromarginatus”, and “medicinal”, “therapeutic”, “benefit”, “effect”, “properties”, bioactive”, “efficacy”, “safety”.

Inclusion and Exclusion Criteria

The following inclusion and exclusion criteria were applied to identify primary articles that reported biological activities and health effects of K. parviflora.

A. Inclusion criteria

Primary literature documenting the biological activities and health effects of K. parviflora as a sole active ingredient, including its representative compounds in all forms (all plant parts and formulations)

Both clinical and preclinical papers

B. Exclusion criteria

Articles on combination products and formulations

No language restrictions were applied.

Data Extraction and Analysis

For the purpose of research gap analysis, the following data were extracted:

Plant part

Formulation details

Pharmacological activity

Disease model

Level of evidence (ie, type of clinical and preclinical study eg, randomized controlled trials, case report, in vivo, in vitro, in silico etc)

Key efficacy findings

Descriptive analysis of the health benefits and biological activities of K. parviflora was performed. Analysis of efficacy focused on the pharmacological actions and level of evidence to identify research gaps and the potential of this plant.

Supplemental Material

sj-docx-1-npx-10.1177_1934578X241281615 - Supplemental material for Application of Kaempferia parviflora: A Perspective Review

Supplemental material, sj-docx-1-npx-10.1177_1934578X241281615 for Application of Kaempferia parviflora: A Perspective Review by Terence Yew Chin Tan, Xin Yi Lim, Puspawathy Krishnan, Siti Hajar Muhamad Rosli, Janice Sue Wen Chan, Yee Lin Voon, Ida Farah Ahmad, Thien Chen Siau, Norizah Awang and Ami Fazlin Syed Mohamed in Natural Product Communications

Footnotes

Acknowledgements

We would like to thank the Director General of Health Malaysia, Deputy Director General of Health Malaysia (Research & Technical Support), Director of Institute for Medical Research, and Head Centre of Herbal Medicine Research Centre for their support and permission to publish this article.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethical Statements

Ethical Approval is not applicable for this article. This article does not contain any studies with human or animal subjects. There are no human subjects in this article and informed consent is not applicable.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iDs

Xin Yi Lim

Puspawathy Krishnan

Siti Hajar Muhamad Rosli

Supplemental Material

Supplemental material for this article is available online.

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